Temporal and institutional trends in robotic surgery.

Robotic surgery has become increasingly prevalent in general surgery practice. While previous studies have shown the safety and efficacy of robotic assistance in laparoscopic general surgery procedures, few studies have evaluated the temporal and regional trends in implementation. In our retrospective population-based study, we aim to evaluate the national trends in robotic surgery. National Inpatient Database (NIS 2009-2014) was used to identify adults who underwent robotic assisted surgery (ICD 9 codes 17.41 to 17.49). Robotic procedures related to seven abdominal organ systems were compared against the trends of Urology, Gynaecologic, and Orthopedic robotic procedures. Discharge weights were applied to calculate National temporal trends separated by hospital size, teaching status and US geographic region. 894,163 patients received a robotic assisted procedure between 2009 and 2014 with 64% increase in utilization. The largest percent change was witnessed in biliary robotic procedures with 2984% change in utilization, followed by hernia (1376%). Lowest percent change was witnessed in esophageal procedures with 114% increase. Medium sized hospitals had the largest change in robotic utilization (41%), with large institutions seeing 18% decrease. Gastric procedures were the most common robotic procedure performed at small institutions (7917 total cases; 316%). Large institutions saw an overall decrease in gastric (- 47%), esophageal (- 17%), small and large intestinal (-16%), and hepatic (- 7%) robotic procedures. Rural non-teaching hospitals saw the largest increase in robotic surgery (274%). Urban non-teaching hospitals saw a decrease of 29%. While urban teaching institutions saw a 20% and 6% increase in gynecological and urological procedures, an overall decrease was seen in esophageal (- 10%), gastric (- 12%), intestinal (- 11%), hepatic (- 17%), biliary (- 10%), pancreatic (- 11%) and hernia procedures (- 14%). Biliary procedures saw the largest increase in rural institutions (740 cases; 392%), followed by hernia (144% increase). South region of the nation had the largest increase in robotic procedures (23%). No change was seen in the use of robotic surgery in the northeast region with the midwest and west seeing an overall decrease (- 4% and - 22%, respectively). Our study highlights the increase in use of robotics for both general and specialty surgery, with an increase in utilization over time. Increased incidence of robotic surgery in smaller, rural institutions with overall decrease in larger, urban teaching hospitals suggests increasing comfort in robotic surgery in the community setting. Further studies are necessary to evaluate the factors associated with increased utilization in smaller institutions.

A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium- and long-term efficacy and safety of topical rapamycin.

AIMS: Topical rapamycin is used to reduce facial angiofibromas in patients with tuberous sclerosis (TSC). In the absence of a commercially available preparation, numerous formulations have been tested clinically, although only in the short term. METHODS: The pharmacy at Angers University Hospital (France) produced a cream formulation that was administered to people presenting this genetic disease. We conducted a questionnaire-based survey among 79 patients with TSC about their perceptions regarding the short-, medium- and long-term efficacy and safety of a topical rapamycin preparation in relation to facial angiofibromas. RESULTS: This formulation was very well tolerated and its efficacy was sustained over the long term with a mean treatment duration of 33 months (extremes 1-60). Efficacy was rated ≥ 8/10 by 67.1% of patients while safety was rated ≥ 8/10 by 84.8% of patients. CONCLUSION: This survey supports the safety and efficacy of topical rapamycin in the short-, medium- and long-term in the treatment of facial angiofibromas in a cohort of 79 patients with TSC.

Comparative study of open, laparoscopic and endoscopic treatments of intermediate grade vesicoureteral reflux in children.

BACKGROUND: Low-grade vesicoureteral-reflux (VUR) are rather treated by endoscopic injection, whereas open or laparoscopic procedures are mainly performed for high-grade VURs. Management of intermediate grades is controversial and no study focused on grade III to date. This study aims to compare the results of open, laparoscopic, and endoscopic approaches in children with grade III VUR. METHODS: A multicenter comparative retrospective study included children with grade III VUR operated for febrile urinary tract infections (UTIs) from 2007 to 2016. Children without UTI, with reflux of other grades, neurological bladder, duplex system, posterior urethral valves, and bladder exstrophy were excluded. Success was defined as no recurrence of febrile UTI and was presented as event-free survival curves. RESULTS: Out of 806 children operated of VUR, 171 met the inclusion criteria (114 females). Seventy-seven children (45%) underwent an open Cohen procedure, 35 (21%) a laparoscopic Lich-Gregoir and 59 (34%) a submucosal endoscopic injection according to the centers' preference. The mean follow-up was 64 months (24-132). Groups were not different for age, sex, and circumcision status. Compared to Cohen procedure, recurrences of febrile UTI were more frequent after laparoscopic treatment (p = 0,02, 8/35) and endoscopic treatment (p = 0.001, 16/59). Redosurgery was also more frequent after laparoscopy (n = 2) and endoscopic injection (n = 14) than after open surgery (n = 0, p < 0.001). CONCLUSION: Recurrent febrile UTIs and redosurgery are more frequent after endoscopic and laparoscopic procedures in grade III VUR than open reimplantation. Whether the lower morbidity of laparoscopic or endoscopic approaches balances the risk of recurrent febrile UTI remains to be determined for intermediate grade reflux.

Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France.

BACKGROUND: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. METHOD: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. RESULTS: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae. CONCLUSION: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections.

Naphthalene cytotoxicity in microsomal epoxide hydrolase deficient mice.

Naphthalene (NA) is a ubiquitous pollutant to which humans are widely exposed. 1,2-Dihydro-1,2-dihydroxynaphthalene (NA-dihydrodiol) is a major metabolite of NA generated by microsomal epoxide hydrolase (mEH). To investigate the role of the NA-dihydrodiol and subsequent metabolites (i.e. 1,2-naphthoquinone) in cytotoxicity, we exposed both male and female wild type (WT) and mEH null mice (KO) to NA by inhalation (5, 10, 20 ppm for 4h). NA-dihydrodiol was ablated in the KO mice. High-resolution histopathology was used to study site-specific cytotoxicity, and formation of naphthalene metabolites was measured by HPLC in microdissected airways. Swollen and vacuolated airway epithelial cells were observed in the intra- and extrapulmonary airways of all mice at and below the current OSHA standard (10 ppm). Female mice may be more susceptible to this acute cytotoxicity. In the extrapulmonary airways, WT mice were more susceptible to damage than KO mice, indicating that the metabolites associated with mEH-mediated metabolism could be partially responsible for cytotoxicity at this site. The level of cytotoxicity in the mEH KO mice at all airway levels suggests that non-mEH metabolites are contributing to NA cellular damage in the lung. Our results indicate that the apparent contribution of mEH-dependent metabolites to toxicity differs by location in the lung. These studies suggest that metabolites generated through the mEH pathway may be of minor importance in distal airway toxicity and subsequent carcinogenesis from NA exposure.

The androgen receptor mediates antiapoptotic function in myometrial cells.

During pregnancy, myometrial phenotype is programmed into three characteristic stages referred to as the early proliferative, the midterm hypertrophic, and the late contractile stage. Increased myometrial growth in the early and midterm of pregnancy involves a complex process of cell proliferation, antiapoptosis and differentiation. We have previously demonstrated that the androgen receptor (AR) is required for myometrial cell proliferation by modulating IGF-1 signaling during early pregnancy. Here, we report that AR also exerts its antiapoptotic function in human myometrial cells. Enhanced AR expression protects, whereas AR silencing sensitizes myometrial cells to both intrinsic and extrinsic apoptotic stimuli. AR agonist inhibits, whereas AR antagonist induces myometrial cells to undergo apoptotic cell death. Gene microarray analysis confirms that the central functions of AR in myometrial cells are to regulate cell cycling and apoptosis through three major gene groups involving the epidermal growth factor (EGF) signaling, RNA splicing and DNA repair processes. AR mediates its antiapoptotic function through two distinct pathways. In the receptor-dependent pathway, AR is required for the expression of several protein factors within the EGF signaling pathway. Through the PI3K/Akt pathway, AR enhances the expression of the antiapoptotic protein Mcl-1. In the ligand-dependent pathway, AR agonist triggers the activation of Src kinase, which in turn phosphorylates STAT3 to increase Mcl-1 expression. We conclude from these results that the AR signaling exerts antiapoptotic function in myometrial cells, further supporting its key role in programming of myometrial phenotype.

[Anuric acute renal failure after suprapubic catheterization]. / Insuffisance rénale aiguë anurique après mise en place d'un cathéter sus-pubien.

Percutaneous suprapubic catheterization is an alternative when placement of a urethral catheter is contraindicated or unsuccessful. We report the case of a 3-day-old newborn, who presented anuric acute renal failure secondary to placement of a suprapubic catheter. An excessive length of catheter had been inserted into the bladder and was obstructing the vesicoureteral junctions. Several measures can be taken to prevent this complication, such as systematic measurement of the length inserted into the bladder, use of a catheter with 1cm gradations or recourse to radiopaque material.

[Acute inflammatory polyradiculoneuropathy and membranous glomerulonephritis following Epbstein-Barr virus primary infection in a 12-year-old girl]. / Polyradiculonévrite aiguë et glomérulonéphrite extramembraneuse au décours d'une primo-infection à Epstein-Barr virus chez une patiente de 12 ans.

Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature.

Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection.

Myocardial ischemia-reperfusion injury is a major cause of morbidity and mortality in developed countries. To date, the only treatment of complete ischemia is to restore blood flow; thus the search for new cardioprotective approaches is absolutely necessary to reduce the mortality associated with myocardial ischemia. Ischemia has long been considered to result in necrotic tissue damage but the reduction in oxygen supply can also lead to apoptosis. Therefore, in the last few years, mitochondria have become the subject of growing interest in myocardial ischemia-reperfusion since they are strongly involved in the regulation of the apoptotic process. Indeed, during ischemia-reperfusion, pathological signals converge in the mitochondria to induce permeabilization of the mitochondrial membrane. Two classes of mechanisms, which are not mutually exclusive, emerged to explain mitochondrial membrane permeabilization. The first occurs via a non-specific channel known as the mitochondrial permeability transition pore (mPTP) in the inner and the outer membranes causing disruption of the impermeability of the inner membrane, and ultimately complete inhibition of mitochondrial function. The second mechanism, involving only the outer membrane, induces the release of cell death effectors. Thus, drugs able to block or to limit mitochondrial membrane permeabilization may be cytoprotective during ischemia-reperfusion. The objective of this review is to examine the pharmacological strategies capable of inhibiting mitochondrial membrane permeabilization induced by myocardial ischemia-reperfusion.

Dietary-induced negative energy balance has minimal effects on innate immunity during a Streptococcus uberis mastitis challenge in dairy cows during midlactation.

Ten multiparous Holstein cows were used to determine the effects of negative energy balance (NEB) on the immune response to a Streptococcus uberis (strain O140J) mastitis challenge during midlactation. Before the study, milk from all quarters of each cow was bacteriologically negative, with a composite somatic cell count of <200,000 cells/mL. Cows were paired based on parity, days in milk, and milk yield. At approximately 77 d in milk, half the cows (n = 5) were feed-restricted to 60% of calculated net energy for lactation requirements to induce NEB. Feed restriction lasted 7 d. Control cows (n = 5) were fed the same diet ad libitum (i.e., positive energy balance; PEB). After 5 d, one rear quarter in all cows was inoculated with 5,000 cfu of Strep. uberis. Jugular blood and aseptic quarter milk samples were collected daily until inoculation and every 6 h postinoculation for 36 h. Blood was analyzed for nonesterified fatty acids, beta-hydroxybutyrate, insulin, cortisol, albumin, serum amyloid A (SAA), and haptoglobin (Hp). Periodically throughout the trial period, blood neutrophils were isolated for determination of cell morphology, chemotaxis, and phagocytosis capability in vitro. Quarter milk samples were analyzed for concentrations of SAA, Hp, cytokines (tumor necrosis factor-alpha, IL-10 and IL-1beta), and activity of respiratory burst enzymes (superoxide dismutase and glutathione peroxidase). All cows developed local and systemic signs of mastitis and calculated NEB was similar to that of cows experiencing postpartal NEB. Serum glucose and insulin concentrations increased in both groups after challenge, most likely because of enhanced glycogenolysis and gluconeogenesis; results indicate that immune cell function may be glucose dependent. Serum cortisol concentration was higher in NEB than PEB cows during feed restriction only (before inoculation), and serum albumin concentration was higher in NEB than PEB cows during the infection period. Compared with PEB, cows in NEB had lower SAA concentrations in serum after 5 d of feed restriction but higher SAA concentrations in milk after Strep. uberis challenge. Serum Hp concentration was higher by 36 h postchallenge in NEB than in PEB cows. Phagocytic capability of neutrophils was lower in NEB than in PEB cows at 0 h of infection but decreased in both PEB and NEB cows through 36 h postinfection. Our results indicate that cows subjected to dietary-induced NEB during midlactation had relatively minimal alterations in immune function.

Liver phosphorus content in Holstein-Friesian cows during the transition period.

Hepatic lipidosis and hypophosphatemia are frequently observed in high-yielding periparturient dairy cows. Objectives of this study were to investigate the association of the liver P content with the degree of liver fat accumulation and serum P concentration and to characterize the change in liver P content throughout the transition period. In a cross-sectional study, liver biopsies obtained from 33 Holstein-Friesian cows 14 d postpartum (p.p.) were assayed for total lipid (TLip), triacylglycerol, DNA, P, Mg, K, Na, and Ca content. Serum samples obtained at the time of biopsy were analyzed for indices of liver function and injury and the serum P concentration was determined. From this cross-sectional study, 6 cows were selected for a longitudinal study and liver tissue obtained from the 6 cows on d -65, -30, -14, 1, 14, 28, and 49 relative to calving was assayed. The amounts of P, K, Mg, Na, and Ca were expressed as amount in dry weight (DW), wet weight (WW), nonfat wet weight (NFWW), and indexed to DNA. In the cross-sectional study, P(DW) and P(WW) decreased with increasing TLip, whereas P(NFWW) and P(DNA) were independent of TLip. Values for P(DNA) varied widely, whereas P(NFWW) varied within a narrow range. Stepwise regression analysis revealed the strongest associations between P(DW) and the amount of tissue water (partial R2 = 0.74) and the log to the base 10 of triacylglycerol (partial R2 = 0.05). The P(WW) was associated with the log to the base 10 of triacylglycerol (partial R2 = 0.20), but no associations were found for P(NFWW). These findings indicate that decreased electrolyte content in dry and wet liver tissue with increased liver lipid content is predominantly due to the decrease in tissue water and therefore the distribution volume of electrolytes. In the longitudinal study, P(DW), P(WW), and P(NFWW) were decreased on d 14 p.p. Similar directional decreases were found for K, Mg, and Na, but P was the only electrolyte that was significantly decreased in liver tissue at d 14 p.p. This finding indicates that the P content of liver tissue decreases in early lactation due to a reduction in hepatocellular cytosol volume as well as a decrease in cytosolic P concentration, with the latter having biological relevance. The clinical significance of decreased cytosolic P concentration in the hepatocytes of dairy cows in early lactation remains to be determined.

Successful algorithm for selective liver biopsy in the right hepatic lobe live donor (RHLD).

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

Glutathione depletion is a major determinant of inhaled naphthalene respiratory toxicity and naphthalene metabolism in mice.

Naphthalene (NA) is metabolized to highly reactive intermediates that are primarily detoxified by conjugation to glutathione (GSH). Intraperitoneal administration of naphthalene causes substantial loss of both hepatic and respiratory GSH, yet only respiratory tissues are injured in mice. The liver supplies GSH to other organs via the circulation, making it unclear whether respiratory GSH losses reflect in situ respiratory depletion or decreased hepatic supply. To address this concern, mice were exposed to naphthalene by inhalation (1.5-15 ppm; 2-4 h), thereby bypassing first-pass hepatic involvement. GSH levels and histopathology were monitored during the first 24 h after exposure. Half of the mice were given the GSH depletor diethylmaleate (DEM) 1 hour before naphthalene exposure. Lung and nasal GSH levels rapidly decreased (50-90%) in mice exposed to 15 ppm naphthalene, with cell necrosis throughout the respiratory tract becoming evident several hours later. Conversely, 1.5 ppm naphthalene caused moderate GSH loss and only injured the nasal olfactory epithelium. Neither naphthalene concentration depleted hepatic GSH. Animals pretreated with DEM showed significant GSH loss and injury in nasal and intrapulmonary airway epithelium at both naphthalene concentrations. DEM treatment, perhaps by causing significant GSH loss, decreased water-soluble naphthalene metabolite formation by 48% yet increased NA-protein adducts 193%. We conclude that (1) GSH depletion occurs in airways independent of hepatic function; (2) sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene; and (3) GSH loss precedes injury and increases protein adduct formation.

Chromate reduction at low sulphate concentration in hydrogen-fed bioreactors.

Aimed at developing a bioremediation process to treat Cr(VI)-bearing water at low sulphate concentration in order to reduce excess sulphide production, the highly toxic, mutagenic, and soluble Cr(VI) was reduced to the less toxic and insoluble Cr(III) in 2-litre fixed-bed reactors inoculated with the sulphate-reducing bacterium (SRB) Desulfomicrobium norvegicum, capable of performing direct enzymatic Cr(VI) reduction. H2 was used as the electron source. The fixed-films were developed on three different supports: a PVC cross-flow material, a pozzolana, and a ceramic granulate. The phased experiments began with a progressive increase of the Cr(VI) concentration in the feed to the column reactors, followed by a progressive decrease of the sulphate concentration. Inhibition by Cr(VI) was less pronounced with pozzolana than with the other supports; when the pozzolana column was fed with a medium containing 100 mg l(-1) Cr(VI) and only 250 mg l(-1) sulphate, the lowest residence time that could be applied for complete Cr(VI) reduction was 16 h. The molar ratio between the sulphate and Cr(VI) reduction rates was decreased down to 1.5, suggesting that indirect reaction with HS was not the sole mechanism of Cr(VI) reduction.

[Ambulatory blood pressure monitoring in multicystic dysplastic kidney disease]. / Monitorización ambulatoria de la presión arterial en pacientes con displasia renal multiquística.

OBJECTIVE: To evaluate blood pressure in a group of patients with multicystic dysplastic kidney (MDK) disease through ambulatory blood pressure (ABP) monitoring. PATIENTS AND METHODS: ABP monitoring was performed in 16 patients with MDK disease using a Spacelabs 90207 monitor and an appropriately sized armband. The patients performed their normal daily activities except physical exercise. The activity period was 8:00 am to 8:00 pm and the resting period was midnight to 6:00 am. Patients with a percentage of correct readings of less than 70 % were excluded. The mean systolic and diastolic blood pressures for each period were calculated. Circadian variability was determined by the ratio between mean systolic and diastolic values in the active and resting periods, respectively. The results were compared with ABP values in healthy children. RESULTS: Fourteen patients (mean age 16 3.1 years, range: 6-27.6) were included. No patients with hypertension were found through casual measurement. One patient had daytime systolic hypertension. Five patients presented an abnormal drop in blood pressure during sleep. CONCLUSION: Blood pressure should be monitored in patients with MDK disease. ABP monitoring may detect alterations that can go unnoticed in casual determinations. Further studies with large samples are needed to establish the real prevalence of hypertension in these patients.

Attenuation of liver normothermic ischemia--reperfusion injury by preservation of mitochondrial functions with S-15176, a potent trimetazidine derivative.

We investigated the antiischemic properties of a new compound, S-15176, in an experimental model of rat liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion. Rats were divided into groups, pretreated with different doses of S-15176 (1.25, 2.5, 5 and 10 mg/kg/day by intramuscular injection) or solvent alone, and subjected to the ischemia--reperfusion process. Another group served as the sham-operated controls. Ischemia--reperfusion induced huge alterations of hepatocyte functions, namely, a decrease in ATP content and bile flow, and membrane leakage of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT). These effects were associated with alterations in mitochondrial functions characterized by (1) a decrease in ATP synthesis, (2) a decrease in NAD(P)H levels and mitochondrial membrane potential, and (3) an increase in mitochondrial swelling reflecting the generation of permeability transition. Pretreatment of rats with S-15176 alleviated these deleterious ischemia--reperfusion effects at both the cellular and mitochondrial levels in a dose-dependent manner. The protection of mitochondrial functions was almost complete at a dosage of 10 mg/kg/day. In addition, in vitro, S-15176 totally abolished the swelling of isolated mitochondria induced by a calcium overload with an IC(50) value of 10 microM. These data demonstrate that S-15176 protects mitochondria against the deleterious effects of ischemia-reperfusion and suggest that this protective effect could be related to the inhibition of the mitochondrial permeability transition.

Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation.

Curcumin is a natural compound showing antiproliferative properties. Recent studies suggest that these properties might be due to its ability to induce apoptosis in tumor cells. As mitochondria play a pivotal role in the induction of the apoptotic process, we analyzed the effect of curcumin on mitochondrial function. Curcumin induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling, loss of membrane potential and inhibition of ATP synthesis. These effects were mediated by the opening of the permeability transition pore. Curcumin pore induction involved the oxidation of membrane thiol functions and required the presence of low Ca(2+) concentrations. These data suggest that mitochondria might be a target by which curcumin induces apoptosis of tumor cells.

[Effect of preservation of the kidney on the long-term function following autotransplantation]. / Influence de la conservation d'un rein sur son devenir fonctionnel à long terme dans un modèle d'autotransplantation.

The consequences of ischaemia-reperfusion injury from kidney recipients on delayed graft function and graft survival still remain a matter of debate. Using an autotransplanted pig kidney model, the influence of trimetazidine added to two standard preservation solutions (Euro-Collins and University of Wisconsin) was studied. The renal parameters were analysed over a period of 12 weeks after transplantation. The degree of interstitial fibrosis, and the number of CD4, CD8 and macrophage positive cells were analysed at 2, 4-5 and 11-12 weeks after the transplantation. Glomerular filtration and sodium reabsorption were significantly more improved after cold-flush and preservation with trimetazidine-supplemented solutions than with trimetazidine-free solutions. The cytoprotective action of trimetazidine also reduced interstitial fibrosis and the number of infiltrating CD4 and CD8-positive cells. These results indicate that the condition of cold preservation may influence long-term kidney graft functions and that trimetazidine reduces to a certain extent the degree of interstitial fibrosis.

[Trimetazidine prevents ischemia-reperfusion injury in hepatic surgery under vascular clamping]. / La trimétazidine prévient les lésions d'ischémie-reperfusion de la chirurgie hépatique sous clampage vasculaire.

Clamping the hepatic pedicle (or Pringle's manoeuvre) is frequently used to reduce blood loss during liver surgery. This induces a normothermic ischaemia of the overall liver. In this study we have investigated the anti-ischaemic effect of trimetazidine during surgery on hydatid cysts of the liver requiring vascular clamping of the hepatic pedicle. Seventy-six hepatic pericystectomies were performed under a 40 min normothermic ischaemia. Two randomized groups including 38 patients each received daily either trimetazidine (80 mg/kg, group 1) or placebo (group 2) for 5 days before surgery. The effect of trimetazidine was evaluated on different parameters, the macroscopic appearance of the tissue, the ATP content in liver biopsies obtained before and after 15, 30 and 60 min reperfusion, the activity of the aminotransferase in the plasma and the plasma concentrations of reduced and oxidized gluthatione. No mortality was observed. The duration of hospital stay was reduced for patients treated with trimetazidine (8 +/- 1 days compared with 11 +/- 1.5 days for patients in group 2; p < 0.05). Morbidity rate was lower in group 1 (11 per cent) than in group 2 (18.5 per cent) but the decrease was not significant. Trimetazidine treatment reduced cytolysis (p < 0.05 on day 1, day 3, day 5), increased liver ATP content and limited the increase of reduced and oxidized gluthatione in the plasma during reperfusion. These results suggest that trimetazidine alleviates ischaemia-reperfusion injury during liver surgery and may allow extension of the ischaemic period without damage to the liver.

[Lower pole pedicle in a series of 84 pyelo-ureteral junction syndromes surgically treated in children]. / Le pédicule polaire inférieur dans une série de 84 syndromes de la jonction pyélo-urétérale opérés chez l'enfant.

OBJECTIVE: To evaluate the involvement and consequences of the lower pole pedicle (LPP) associated with ureteropelvic junction syndrome. MATERIAL AND METHOD: Retrospective study in 81 children presenting a total of 84 ureteropelvic junction syndromes operated consecutively between 1994 and 1998. Urinary tract ultrasound and cystography were systematically performed. Renal scintigraphy (DTPA or MAG 3) was performed in 80 children. Preoperative intravenous urography was performed in 60 children. LPP was considered to be present when its participation in the obstruction was confirmed intraoperatively (Anderson Hynes technique with uncrossing of the vascular pedicle). RESULTS: Group I: a LPP was revealed in 24 kidneys (28.5% of cases), 17 left kidneys and 7 right kidneys, in 14 boys and 10 girls, with a mean age of 4 years (range: 2 months-14 years). Group II: 60 kidneys without LPP (71.5% of cases), 32 left kidneys and 28 right kidneys, in 40 boys and 17 girls, with a mean age of 2 years (range: 1 month-15 years). The most frequent presenting complaint was recurrent low back pain in 58% of cases in group I (14/24) and 5% of cases in group II (3/60). The mean age at diagnosis was 6 years. Hydronephrosis was detected by antenatal ultrasound in 33% of cases in group I (8/24) and in 72% of cases in group II (43/60). Kidney function in group I was greater than 40% in 19 patients, between 20 and 39% in 2 patients and less than 20% in 2 patients. These results were not influenced by age at diagnosis and were not significantly different from those observed in group II. Renal malrotation was observed in 2 cases in group I and in 12 cases in group II. Histology of the junction revealed nonspecific fibrosis in the same percentage of cases (91%) in the two groups. The mean follow-up was 15 months (range: 2 months-5 years). No surgical failure was observed. CONCLUSION: Ureteropelvic junction syndrome associated with a LPP appears to present later with recurrent low back pain in older children. It does not worsen the functional prognosis of the affected kidney. LPP can be visualized by duplex ultrasound. It may act as an inducer of obstruction by aggravating a pre-existing abnormality of the ureteropelvic junction. When LPP is associated with isolated dilatation of the pyelocaliceal cavities, the risk of subsequent decompensation requires closer ultrasound surveillance, until puberty.